Subsensory stochastic electrical stimulation targeting muscle afferents alters gait control during locomotor adaptations to haptic perturbations.

Subsensory noise stimulation targeting sensory receptors has been shown to improve balance control in healthy and impaired individuals. However, the potential for application of this technique in other contexts is still unknown. Gait control and adaptation rely heavily on the input from proprioceptive organs in the muscles and joints. Here we investigated the use of subsensory noise stimulation as a means to influence motor control by altering proprioception during locomotor adaptations to forces delivered by a robot. The forces increase step length unilaterally and trigger an adaptive response that restores the original symmetry. Healthy participants performed two adaptation experiments, one with stimulation applied to the hamstring muscles and one without. We found that participants adapted faster but to a lesser extent when undergoing stimulation. We argue that this behavior is because of the dual effect that the stimulation has on the afferents encoding position and velocity in the muscle spindles.

Minimally instrumented SHERLOCK (miSHERLOCK) for CRISPR-based point-of-care diagnosis of SARS-CoV-2 and emerging variants.

The COVID-19 pandemic highlights the need for diagnostics that can be rapidly adapted and deployed in a variety of settings. Several SARS-CoV-2 variants have shown worrisome effects on vaccine and treatment efficacy, but no current point-of-care (POC) testing modality allows their specific identification. We have developed miSHERLOCK, a low-cost, CRISPR-based POC diagnostic platform that takes unprocessed patient saliva; extracts, purifies, and concentrates viral RNA; performs amplification and detection reactions; and provides fluorescent visual output with only three user actions and 1 hour from sample input to answer out. miSHERLOCK achieves highly sensitive multiplexed detection of SARS-CoV-2 and mutations associated with variants B.1.1.7, B.1.351, and P.1. Our modular system enables easy exchange of assays to address diverse user needs and can be rapidly reconfigured to detect different viruses and variants of concern. An adjunctive smartphone application enables output quantification, automated interpretation, and the possibility of remote, distributed result reporting.

Wearable materials with embedded synthetic biology sensors for biomolecule detection.

Integrating synthetic biology into wearables could expand opportunities for noninvasive monitoring of physiological status, disease states and exposure to pathogens or toxins. However, the operation of synthetic circuits generally requires the presence of living, engineered bacteria, which has limited their application in wearables. Here we report lightweight, flexible substrates and textiles functionalized with freeze-dried, cell-free synthetic circuits, including CRISPR-based tools, that detect metabolites, chemicals and pathogen nucleic acid signatures. The wearable devices are activated upon rehydration from aqueous exposure events and report the presence of specific molecular targets by colorimetric changes or via an optical fiber network that detects fluorescent and luminescent outputs. The detection limits for nucleic acids rival current laboratory methods such as quantitative PCR. We demonstrate the development of a face mask with a lyophilized CRISPR sensor for wearable, noninvasive detection of SARS-CoV-2 at room temperature within 90 min, requiring no user intervention other than the press of a button.

Sensory enhancing insoles improve athletic performance during a hexagonal agility task.

Athletes incorporate afferent signals from the mechanoreceptors of their plantar feet to provide information about posture, stability, and joint position. Sub-threshold stochastic resonance (SR) sensory enhancing insoles have been shown to improve balance and proprioception in young and elderly participant populations. Balance and proprioception are correlated with improved athletic performance, such as agility. Agility is defined as the ability to quickly change direction. An athlete's agility is commonly evaluated during athletic performance testing to assess their ability to participate in a competitive sporting event. Therefore, the purpose of this study was to examine the effects of SR insoles during a hexagonal agility task routinely used by coaches and sports scientists. Twenty recreational athletes were recruited to participate in this study. Each athlete was asked to perform a set of hexagonal agility trials while SR stimulation was either on or off. Vicon motion capture was used to measure feet position during six successful trials for each stimulation condition. Stimulation condition was randomized in a pairwise fashion. The study outcome measures were the task completion time and the positional accuracy of footfalls. Pairwise comparisons revealed a 0.12s decrease in task completion time (p=0.02) with no change in hopping accuracy (p=0.99) when SR stimulation was on. This is the first study to show athletic performance benefits while wearing proprioception and balance improving equipment on healthy participants. With further development, a self-contained sensory enhancing insole device could be used by recreational and professional athletes to improve movements that require rapid changes in direction.

Sensory Enhancing Insoles Modify Gait during Inclined Treadmill Walking with Load.

INTRODUCTION: Inclined walking while carrying a loaded backpack induces fatigue, which may destabilize gait and lead to injury. Stochastic resonance (SR) technology has been used to stabilize spatiotemporal gait characteristics of elderly individuals but has not been tested on healthy recreational athletes. Herein, we determined if sustained vigorous walking on an inclined surface while carrying a load destabilizes gait and if SR has a further effect. METHODS: Participants were fitted with a backpack weighing 30% of their body weight and asked to walk at a constant self-selected pace while their feet were tracked using an optical motion capture system. Their shoes were fitted with SR insoles that were set at 90% of the participant's sensory threshold. The treadmill incline was increased every 5 min until volitional exhaustion after which the treadmill was returned to a level grade. SR stimulation was turned ON and OFF in a pairwise random fashion throughout the protocol. Spatiotemporal gait characteristics were calculated when SR was ON and OFF for the BASELINE period, the MAX perceived exertion period, and the POST period. RESULTS: Vigorous activity increases variability in the rhythmic stepping (stride time and stride length) and balance control (double support time and stride width) mechanisms of gait. Overall, SR increased stride width variability by 9% before, during, and after a fatiguing exercise. CONCLUSION: The increased stride time and stride length variability may compromise the stability of gait during and after vigorous walking. However, participants may compensate by increasing double support time and stride width variability to maintain their stability under these adverse conditions. Furthermore, applying SR resulted in an additional increase of stride width variability and may potentially improve balance before, during, and after adverse walking conditions.

A shoe insole delivering subsensory vibratory noise improves balance and gait in healthy elderly people.

OBJECTIVES: To test whether subsensory vibratory noise applied to the sole of the foot using a novel piezoelectric vibratory insole can significantly improve sensation, enhance balance, and reduce gait variability in elderly people, as well as to determine the optimal level of vibratory noise and whether the therapeutic effect would endure and the user's sensory threshold would remain constant during the course of a day. DESIGN: A randomized, single-blind, crossover study of 3 subsensory noise stimulation levels on 3 days. SETTING: Balance and gait laboratory. PARTICIPANTS: Healthy community-dwelling elderly volunteers (N=12; age, 65-90y) who could feel the maximum insole vibration. INTERVENTIONS: A urethane foam insole with the piezoelectric actuators delivering subsensory vibratory noise stimulation to the soles of the feet. MAIN OUTCOME MEASURES: Balance, gait, and timed Up and Go (TUG) test. RESULTS: The vibratory insoles significantly improved performance on the TUG test, reduced the area of postural sway, and reduced the temporal variability of walking at both 70% and 85% of the sensory threshold and during the course of a day. Vibratory sensation thresholds remained relatively stable within and across study days. CONCLUSIONS: This study provides proof of concept that the application of the principle of stochastic resonance to the foot sole sensory system using a new low-voltage piezoelectric technology can improve measures of balance and gait that are associated with falls. Effective vibratory noise amplitudes range from 70% to 85% of the sensory threshold and can be set once daily.

Baseline-dependent effect of noise-enhanced insoles on gait variability in healthy elderly walkers.

The purpose of this study was to determine whether providing subsensory stochastic-resonance mechanical vibration to the foot soles of elderly walkers could decrease gait variability. In a randomized double-blind controlled trial, 29 subjects engaged in treadmill walking while wearing sandals customized with three actuators capable of producing stochastic-resonance mechanical vibration embedded in each sole. For each subject, we determined a subsensory level of vibration stimulation. After a 5-min acclimation period of walking with the footwear, subjects were asked to walk on the treadmill for six trials, each 30s long. Trials were pair-wise random: in three trials, actuators provided subsensory vibration; in the other trials, they did not. Subjects wore reflective markers to track body motion. Stochastic-resonance mechanical stimulation exhibited baseline-dependent effects on spatial stride-to-stride variability in gait, slightly increasing variability in subjects with least baseline variability and providing greater reductions in variability for subjects with greater baseline variability (p<.001). Thus, applying stochastic-resonance mechanical vibrations on the plantar surface of the foot reduces gait variability for subjects with more variable gait. Stochastic-resonance mechanical vibrations may provide an effective intervention for preventing falls in healthy elderly walkers.

Stochastic resonance stimulation for upper limb rehabilitation poststroke.

OBJECTIVES: Previous studies have shown that subthreshold electrical or mechanical noise can reduce the sensory threshold and impart short-term improvements in sensorimotor function. We undertook this study to examine the effects of combined subsensory electrical and vibratory stimulation in conjunction with exercise training on long-term motor performance. DESIGN: Thirty subjects were recruited from adult community-dwelling stroke survivors with residual hemiparesis. Subjects were screened for residual motor ability using a functional task, and those who functioned below this level were excluded. All subjects had a history of a single unilateral ischemic or hemorrhagic stroke at least 6 mos before study entry and were not actively receiving occupational or physical therapy. Subjects were stratified by baseline upper extremity Fugl-Meyer (UEFM) (more impaired [28-35] and less impaired [36-55]) and were randomized to one of two groups: treatment (stochastic resonance stimulation [plus over minus sign] exercise: 15 subjects) and control (sham stimulation [plus over minus sign] exercise: 15 subjects). RESULTS: No significant difference was found between the stochastic resonance treatment and control group in the UEFM or in any of the secondary measures. The combined group showed modest improvements in UEFM from baseline to completion of therapy (mean improvement, 2.6 points) (P = 0.004); however, these improvements declined by 1-mo follow-up to 1.5 points (P = 0.055). No change in sensory function was detectable. CONCLUSIONS: Stochastic resonance therapy combined with occupational therapy was no more effective than occupational therapy alone in restoring sensorimotor performance. Other stochastic resonance stimulation montages or protocols might prove more effective.

Prolonged mechanical noise restores tactile sense in diabetic neuropathic patients.

Acute application of stochastic resonance (SR), defined as a subsensory level of mechanical noise presented directly to sensory neurons, improves the vibration and tactile perception in diabetic patients with mild to moderate neuropathy. This study examined the effect of 1 hour of continuous SR stimulation on sensory nerve function. Twenty diabetic patients were studied. The effect of stimulation was measured at 2 time points, at the beginning and after 60 minutes of continual SR stimulation. This effect was measured using the vibration perception threshold (VPT) at the big toe under 2 conditions: a null (no SR) condition and active SR, defined as mechanical noise below the subject's own threshold of perception. The measurements under null and active conditions were done randomly and the examiner was blinded regarding the type of condition. Immediately after SR application, the VPT with SR in null condition was similar to baseline (32.2 +/- 13.1, P = nonsignificant) but was significantly lower during active SR (27.4 +/- 11.9) compared with both baseline (P = .018) and off position (P = .045). The 60 minutes VPT with active SR (28.7 +/- 11.1) reached significance comparing the baseline when one outlier was removed from the analysis (P = .031). It may be concluded that SR for a continuous 60-minute period can sustain the VPT improvement in diabetic patients with moderate to severe neuropathy. These results permit the conclusion that there is no short-term adaptation to the stimulation signal. Long-term application of this technique, perhaps in the form of a continually vibrating shoe insert, or insole, may result in sustained improvement of nerve function.

Noise-enhanced balance control in patients with diabetes and patients with stroke.

OBJECTIVE: Somatosensory function declines with diabetic neuropathy and often with stroke, resulting in diminished motor performance. Recently, it has been shown that input noise can enhance human sensorimotor function. The goal of this study was to investigate whether subsensory mechanical noise applied to the soles of the feet via vibrating insoles can be used to improve quiet-standing balance control in 15 patients with diabetic neuropathy and 15 patients with stroke. Sway data of 12 healthy elderly subjects from a previous study on vibrating insoles were added for comparison. METHODS: Five traditional sway parameters and three sway parameters from random-walk analysis were computed for each trial (no noise or noise). RESULTS: Application of noise resulted in a statistically significant reduction in each of the eight sway parameters in the subjects with diabetic neuropathy, the subjects with stroke, and the elderly subjects. We also found that higher levels of baseline postural sway in sensory-impaired individuals was correlated with greater improvements in balance control with input noise. INTERPRETATION: This work indicates that noise-based devices could ameliorate diabetic and stroke impairments in balance control.

Enhancing sensation in diabetic neuropathic foot with mechanical noise.

OBJECTIVE: Localized low-level mechanical or electrical noise can significantly enhance tactile sensitivity in healthy young subjects and older adults. This phenomenon is termed stochastic resonance (SR). In this study, we examined the effect of SR on vibratory and tactile sensation in patients with moderate to severe diabetic peripheral neuropathy. RESEARCH DESIGN AND METHODS: A total of 20 subjects were included in the study. The vibration perception threshold (VPT) test and the Semmes-Weinstein filament (SWF) threshold at the plantar surface of the left foot and the big toe were determined under two mechanical noise stimulus conditions: null (no noise) condition and at 10% lower than each subject's mechanical noise threshold of perception. RESULTS: The baseline values (mean +/- SD) were as follows: Neuropathy Symptom Score (NSS) 5.2 +/- 2.5, Neuropathy Disability Score (NDS) 5.0 +/- 2.1, VPT 24 +/- 11 V, and SWF threshold 5.6 +/- 0.8 at the plantar surface of the foot and 5.3 +/- 0.9 at the big toe. The VPT improved significantly from 24 +/- 11 under null condition to 19 +/- 10 V with mechanical noise (P < 0.0001). Mechanical noise also significantly increased the number of detections of the SWF at the plantar surface of the foot (detection rate 66 +/- 11 vs. 59 +/- 15%, P < 0.02) but not at the big toe (63 +/- 10 vs. 61 +/- 16%, P = NS). CONCLUSIONS: Mechanical noise stimulation improves vibration and tactile perception in diabetic patients with moderate to severe neuropathy. Additional studies are required to examine the effect of long-term noise stimulation on parameters of nerve function.

Vibrating insoles and balance control in elderly people.

Somatosensory function declines with age, and such changes have been associated with diminished motor performance. Input noise can enhance sensory and motor function. We asked young and elderly participants to stand quietly on vibrating gel-based insoles, and calculated sway parameters and random-walk variables. In our 27 participants, application of noise resulted in a reduction in seven of eight sway parameters in young participants and all of the sway variables in elderly participants. Elderly participants showed greater improvement than young people in two variables, mediolateral range (p=0.008), and critical mean square displacement (p=0.012). Noise-based devices, such as randomly vibrating insoles, could ameliorate age-related impairments in balance control.

Noise-enhanced human balance control.

Noise can enhance the detection and transmission of weak signals in certain nonlinear systems, via a mechanism known as stochastic resonance. Here we show that input noise can be used to improve motor control in humans. Specifically, we show that the postural sway of both young and elderly individuals during quiet standing can be significantly reduced by applying subsensory mechanical noise to the feet. We further demonstrate with input noise a trend towards the reduction of postural sway in elderly subjects to the level of young subjects. These results suggest that noise-based devices, such as randomly vibrating shoe inserts, may enable people to overcome functional difficulties due to age-related sensory loss.

Noise-enhanced balance control in older adults.

Somatosensory information is critical to balance control and fall prevention in older adults. Recently, it has been shown that low-level input noise (electrical or mechanical) can enhance the sensitivity of the human somatosensory system. In this study, we tested the effect of low-level electrical noise, applied at the knee, on balance control in 13 healthy elderly volunteers. Subjects performed multiple single-legged stance trials with imperceptible electrical noise applied at the knee during half of the trials. Balance performance was characterized using a force platform to measure the displacement of the center of pressure (COP) under the subject's stance foot. Seven sway parameters were extracted from the COP time series. Improved balance was defined as a reduction in postural sway as indicated by decreases in the COP measures. Six of the seven sway parameters decreased with electrical noise. Three of these parameters decreased significantly ( < 0.05), and a fourth parameter was borderline significant. Averaged across subjects, the application of electrical noise resulted in a 3.8% reduction in mediolateral COP standard deviation ( = 0.04), a 5.4% decrease in the maximum anteroposterior COP excursion ( = 0.03), a 3.1% reduction in the COP path length ( = 0.04), and a 7.8% decrease in swept area ( = 0.05). The results suggest that imperceptible electrical noise, when applied to the knee, can enhance the balance performance of healthy older adults. These findings suggest that electrical noise-based devices may be effective in improving balance control in elderly people.

Enhancing tactile sensation in older adults with electrical noise stimulation.

Older adults often suffer from diminished somatosensation stemming from age-related neuropathy. Recently, localized low-level electrical noise stimulation was shown to enhance tactile sensitivity in healthy young subjects. Here, we hypothesized that fine-touch sensitivity in older adults can be similarly improved. Semmes-Weinstein monofilaments were used to evaluate fine-touch sensitivity on the first metatarsal phalangeal joint with four electrical stimulus conditions and a null (no-noise) condition in nine healthy elderly subjects. Electrical noise stimulation resulted in a statistically significant increase in the number of detections below the null-condition detection threshold, for five of the nine subjects, as well as across the entire population. This work suggests that electrical noise-based techniques may enable people to overcome functional difficulties due to age-related sensory loss.